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粪类圆线虫 L3i 幼虫转录组分析揭示了在被忽视疾病中进行干预的靶点。

The transcriptome analysis of Strongyloides stercoralis L3i larvae reveals targets for intervention in a neglected disease.

机构信息

Área de Parasitología, Departamento de Biologia Celular y Parasitología, Universitat de València, Burjassot, Valencia, Spain.

出版信息

PLoS Negl Trop Dis. 2012;6(2):e1513. doi: 10.1371/journal.pntd.0001513. Epub 2012 Feb 28.

Abstract

BACKGROUND

Strongyloidiasis is one of the most neglected diseases distributed worldwide with endemic areas in developed countries, where chronic infections are life threatening. Despite its impact, very little is known about the molecular biology of the parasite involved and its interplay with its hosts. Next generation sequencing technologies now provide unique opportunities to rapidly address these questions.

PRINCIPAL FINDINGS

Here we present the first transcriptome of the third larval stage of S. stercoralis using 454 sequencing coupled with semi-automated bioinformatic analyses. 253,266 raw sequence reads were assembled into 11,250 contiguous sequences, most of which were novel. 8037 putative proteins were characterized based on homology, gene ontology and/or biochemical pathways. Comparison of the transcriptome of S. strongyloides with those of other nematodes, including S. ratti, revealed similarities in transcription of molecules inferred to have key roles in parasite-host interactions. Enzymatic proteins, like kinases and proteases, were abundant. 1213 putative excretory/secretory proteins were compiled using a new pipeline which included non-classical secretory proteins. Potential drug targets were also identified.

CONCLUSIONS

Overall, the present dataset should provide a solid foundation for future fundamental genomic, proteomic and metabolomic explorations of S. stercoralis, as well as a basis for applied outcomes, such as the development of novel methods of intervention against this neglected parasite.

摘要

背景

旋毛虫病是全球分布最广泛的被忽视疾病之一,在发达国家存在地方性流行,慢性感染可危及生命。尽管其影响很大,但人们对涉及的寄生虫的分子生物学及其与宿主的相互作用知之甚少。下一代测序技术现在为快速解决这些问题提供了独特的机会。

主要发现

在这里,我们使用 454 测序结合半自动生物信息学分析,首次展示了 S. stercoralis 第三期幼虫的转录组。253266 个原始序列读取被组装成 11250 个连续序列,其中大多数是新的。基于同源性、基因本体和/或生化途径,对 8037 个推定蛋白进行了特征描述。将 S. strongyloides 的转录组与其他线虫(包括 S. ratti)的转录组进行比较,发现与寄生虫-宿主相互作用中具有关键作用的分子的转录具有相似性。酶蛋白,如激酶和蛋白酶,很丰富。使用包括非经典分泌蛋白在内的新管道,共编译了 1213 种推定的排泄/分泌蛋白。还确定了潜在的药物靶点。

结论

总的来说,本数据集应为未来对 S. stercoralis 的基础基因组、蛋白质组学和代谢组学的探索提供坚实的基础,也为应用结果(如针对这种被忽视寄生虫的新干预方法的开发)提供了基础。

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